CT-Luso intends to (1) draw an updated diagnosis and screenshot of the research ethics infrastructure in the 5 Portuguese-speaking African Countries (PSAC), (2) identify the needed transformations, draft strategic recommendations to carry out this transformation and design a policy roadmap for its implementation, (3) reinforce existing legislation and promote the necessary regulations for a robust ethical-legal framework, supporting the revision of internal regulations for the operation of RECs and NRAs, and promote the development of codes of scientific integrity in research institutions, (4) strengthen the skills of RECs and NRAs, researchers (senior, junior and post-graduate students) by drafting guidelines for the practice of the different roles required by the evaluation of CTs. It is necessary to work with all 5 PSAC simultaneously on four different levels, all equally indispensable and complementary: legislative, institutional, professional, and procedural, which in turn requires political commitment. CT-Luso proposes to reach the abovementioned objectives by (1) building an international team of legal experts and promoting dialogue for the co-creation of legislative and organizational recommendations (2) creating an interdisciplinary and cross-sectoral education (3) creating an advanced progressive training program for members of RECs, NRA, CTs Centres and researchers (4) hands-on experience developed in a finely tuned manner and according to country specificities, complementing the previous education and training programs (5) assess whether each PSAC has the necessary installed capacity to be included in the international CTs roadmap and in particular to create a Portuguese-speaking cluster by simulating the procedures under the development of an academic CT (6) in parallel, the legislative and regulatory transformations to be implemented will require the political power involvement, acting in a double approach, both bottom-up and top-down.

Childhood tuberculosis (TB) remains globally underdiagnosed and untreated. In 2022, WHO conditionally recommended the use of treatment decision algorithms (TDAs) to improve the diagnosis of pulmonary TB in children <10 years and called for the external validation of two suggested TDAs for children. The Decide-TB project aims to generate evidence for the implementation of a comprehensive TDA-based approach for TB in children living in high-burden, resource-limited countries, at district hospital and primary health centre levels, and to facilitate the integration of this evidence into practice and policy. As an interdisciplinary consortium of researchers and national TB programs (NTPs), we will conduct a programmatic pilot of WHO-suggested TDAs, also integrating specific TDAs for children living with HIV and/or those malnourished, and severity assessment for shorter treatment decision in non-severe TB disease. Clinical mentoring tools and a Clinical Decision Support System will be developed. District information systems will be strengthened to collect individual data for program monitoring and supervision by NTPs, and for research. The TDA-based approach will be tested in a pragmatic stepped wedge cluster-randomized trial, including effectiveness, implementation, socio-behavioural, economics and policy research components. The diagnostic accuracy of TDAs will be assessed in a parallel meta-analysis of children with presumptive TB from recent studies led by consortium members. The pragmatic trial and meta-analysis will contribute to external validation of the WHO-suggested TDAs. Engagement of key stakeholders and decision-makers throughout the project will support adoption into international and national policies and into clinical practice. Through validation of TDAs, widespread policy adoption, and translation into clinical practice, Decide-TB will increase access to safe and effective TB management for children, thus reduce TB mortality and contribute to SDG3.